Process of making the n-propyl ester of p-aminobenzoic acid.



- This increased anesthetic action is UNITED STATES PATENT OFFICE.

RICHARD LTTTDERS, F HAMBURG, GERMANY.

PROCESS OF MAKING; THE N-PROPYL ESTER OF"P-AMINOBENZOIC ACID.

aaonse.

No Drawing.

To all ivhom it may concern:

Be it known that l, RICHARD Li'mnns,

of the n-amino-p-oxybenzoic acid, have ananesthetic action; It has been now found that by introducing n-propyl in place of methyl or ethyl into the carboxyl group of aminobenzoic acids,

the anesthetic action of the esters is increased.

more particularly to be found in the hitherto unknown n-propyl-ester of the p-aminobenzoic acid while the use of still higher aliphatic alcohols does not strengthen the anesthetic action, but on the contrary the higher molecular alkyl esters of the p-aminobenzoic acid have the disadvantage of being more poisonous. Nor is the anesthetic action in any way increased by the introduction of hydroaromatic or aromatic esters of such alcohols or phenols which in themselves have an anesthetic action, such as for, instance-menthol, guajacol, or thymol, into the molecule of the p-aminobenzoic acid.

The process for manufacturing p-aminobenzoic-acidn-propyl ester is carried out in a manner similar to that for manufacturing methyl and ethyl esters of the p-aminobenzoic acid, that is to say, either by converting p-aminobenzoic acid into an ester by means of n-propyl alcohol, or by the treatment of p-nitrobenzoic acid-n-propyl ester with re-.

ducing agents.

Ewa-mples. v 1. 5 parts by Weight of 'n-propyl alcohol are boiled with 1 art of p-nitrobenzoic acid and 1 part of sul ric acid or similar water absorbmg means, until the com lete conversion into ester takes place". T e excess of alcohol is removed b distillation, the sulfuric acid neutralized by sodium carbonate or any similar alkaline agent, and the pnitrobenzoic acid-n-propyl ester which is insoluble, separated. This ester has a'melt ing point of about 35 C. after having been purified by recrystallization by means of alcohol. This hitherto unknown. n-propyl Specification of Letters Patent.

Patented Mar. 1, 1910.

Application filed January 27, 1909. Serial No. 74,478.v (Specimens) of the nitro group. After the reduction,

soda is added untll an alkaline reaction is obtained. The whole mass is then lixiviated with ether or benzol, which dissolves out the p-aminobenzoic-acidn propyl ester. The solution is then separated from the solid residue by filtration or decantation and then heated in a closed vessel, whereupon the ether or benzol vaporizes, leavlng the slightly im ure ester. This is then dissolved in ether and allowed to crystallize, the crystals being then redissolved in ether and allowed to crystallize again. This recrystallization is repeated until the ester is pure, at which time its melting point is about '7 3 or 74 (1, and is in the form of needle crystals.

2. Connersz'on into esters of the p-amz'nobenzoz'e acid with n-propyl aZc0h0Z.Either 1 part of the -amin0benzoic acid is boiled with 5' arts of n-propyl alcoholin the presence o sulfuric acid, or dry hydrochloric acid gas is introduced into the mixture of p-aminobcuzoic acid and n-propyl alcohol, until a large portion of the p-aminobenzoic acid has been converted into ester. After the reaction is completed, the sulfuric or hydrochloric acid is neutralized, and the excess of n-propyl alcohol removed by distillation. The residue is treated with diluted cold soda lye until the p-aminobenzoic acid that has not been converted into ester, is dissolved. The remainingaester is crystallized from benzol until it is pure.

The product obtained in the manner hereinbefore described,'is the u-propyl ester of the p-aminobenzoic acid and, as proved by physiological comparative experiments, has a stronger anesthetic action than the p-aminobenzoic acid-ethyl ester (anesthesin) and the n-amino-p-oxybenzoicanethyl ester (new ortho form). It can easily be dissolved in benzol, alcohol and similar organic solvents, but is very little soluble in Water.

The melting point of the n-propyl ester of the p-aminobenzoic acid is 73-74 G, and

it crystallizes in colorless rhombic prisms haviiig the brilliancy of glass to mother of pear The n-propyl ester of p-aminobenzoic acid is intended to be used for physiological purposes and for the manufacture of cosmetic, hygienic or therapeutical preparations.

The formed y fp-nitrobenzoic acid and n-propyl alcohol as ollows:

N0 NH:

coocsm 00008111 cmmo, COgCgHri-GH:C.H .NHg-CO C;H1+2H O. I claim 1. The herein described process, which nitrobenzoic n propyl ester is consists in preparing p-nitrobenzoic-n-propyl ester, treating this ester with a nitroreducing means, adding an alkaline a ent, treating the mass with ether, and crysta lizing out p-aminobenzoic-n-propyl ester, substantially as described,

2. The herein described process, which 40 consists in boiling 5 parts of n-propyl alcohol with 1 part of p-nitrobenzoic acid and 1 part sulfuric-acid, removing the excess of alcohol, neutralizing the sulfuric acid, separating from the resultant mass p-nitrobenzoic-nropyl ester, boiling said ester with 1 part 0 tin and 3 parts of hydrochloric acid, adding an alkaline agent, lixiviating the resultant mass with ether, and crystallizing out from theether solution p-aminobenzoicn-propyl ester, substantially as described.

3. The herein described p-aminobenzoic-npropyl ester, crystallizin 1n colorless rhombic crystals, soluble in enzol and alcohol, almost insoluble in water, melting at 7374 C. and having strong anesthetic properties, substantially as described.

In testimony, that I claim the foregoing as my invention, I have signed my name in presence of two witnesses, this ninth day of January 1909.

RICHARD LUDERSQ Witnesses:

FRANZ O. Fm'rzscnn, JOHANNES F. SUHR. 

